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An automated Design-Build-Test-Learn pipeline for enhanced microbial production of fine chemicals
Open accessAbstract
The microbial production of fine chemicals provides a promising biosustainable manufacturing solution that has led to the successful production of a growing catalog of natural products and high-value chemicals. However, development at industrial levels has been hindered by the large resource investments required. Here we present an integrated Design–Build-Test–Learn (DBTL) pipeline for the discovery and optimization of biosynthetic pathways, which is designed to be compound agnostic and automated throughout. We initially applied the pipeline for the production of the flavonoid (2 S)-pinocembrin in Escherichia coli, to demonstrate rapid iterative DBTL cycling with automation at every stage. In this case, application of two DBTL cycles successfully established a production pathway improved by 500-fold, with competitive titers up to 88 mg L−1. The further application of the pipeline to optimize an alkaloids pathway demonstrates how it could facilitate the rapid optimization of microbial strains for production of any chemical compound of interest.
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Cites
Construction of Escherichia coli K‐12 in‐frame, single‐gene knockout mutants: the Keio collection
Baba, T., Ara, T., Hasegawa, M., Takai, Y., Okumura, Y., Baba, M., Datsenko, K. A., Tomita, M., Wanner, B. L., & Mori, H. (2006) · Molecular Systems Biology · doi:10.1038/msb4100050 · Cited by 7,858
Cited by
Self-Driving Laboratories for Chemistry and Materials Science
Tom, G., Schmid, S. P., Baird, S. G., Cao, Y., Darvish, K., Hao, H., Lo, S., Pablo-García, S., Rajaonson, E. M., Skreta, M., et al. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00055 · Cited by 707
Synthetic biology strategies for microbial biosynthesis of plant natural products
Cravens, A., Payne, J., & Smolke, C. D. (2019) · Nature Communications · doi:10.1038/s41467-019-09848-w · Cited by 438
Embracing Nature’s Catalysts: A Viewpoint on the Future of Biocatalysis
Hauer, B. (2020) · ACS Catalysis · doi:10.1021/acscatal.0c01708 · Cited by 284
An Automated Model Test System for Systematic Development and Improvement of Gene Expression Models
Reis, A. C., & Salis, H. M. (2020) · ACS Synthetic Biology · doi:10.1021/acssynbio.0c00394 · Cited by 166
Metadata
- Authors
- Carbonell, P., Jervis, A. J., Robinson, C. J., Yan, C., Dunstan, M., Swainston, N., Vinaixa, M., Hollywood, K. A., Currin, A., Rattray, N. J. W., Taylor, S., Spiess, R., Sung, R., Williams, A. R., Fellows, D., Stanford, N. J., Mulherin, P., Le Feuvre, R., Barran, P., Goodacre, R., Turner, N. J., Goble, C., Chen, G. G., Kell, D. B., Micklefield, J., Breitling, R., Takano, E., Faulon, J.-L., & Scrutton, N. S.
- Venue
- Communications Biology
- Published
- 2018-06-08
- Volume
- 1
- Issue
- 1
- Pages
- 66-66
- ISSN
- 2399-3642 (ISSN-L)
- OpenAlex
- W2806394571
- Cited by
- 288
- References
- 1
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- gold
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- Carbonell, P., Jervis, A. J., Robinson, C. J., Yan, C., Dunstan, M., Swainston, N., Vinaixa, M., Hollywood, K. A., Currin, A., Rattray, N. J. W., Taylor, S., Spiess, R., Sung, R., Williams, A. R., Fellows, D., Stanford, N. J., Mulherin, P., Le Feuvre, R., Barran, P., . . . Scrutton, N. S. (2018). An automated Design-Build-Test-Learn pipeline for enhanced microbial production of fine chemicals. Communications Biology. https://doi.org/10.1038/s42003-018-0076-9
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